Miniature LED implant shines light on workings of mouse brain

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A miniature electronic device with LEDs the size of neurons when
implanted in the brain of a genetically altered mouse can stimulate
the release of dopamine, a chemical associated with pleasure.

The researchers, at Washington University School of Medicine in
St. Louis and the University of Illinois at Urbana-Champaign report
their findings in the journal Science [1].

For the study, Washington University neuroscientists teamed with
engineers at the University of Illinois to design microscale LED
devices thinner than a human hair. This was the first application of
the devices in optogenetics, an area of neuroscience that uses light
to stimulate targeted pathways in the brain. The scientists
implanted them into the brains of mice that had been genetically
engineered so that some of their brain cells could be activated and
controlled with light.

This implantable LED light can activate brain
cells to releasedopamine and is smaller than the eye of a
needle.

“This strategy should allow us to identify and map brain circuits
involved in complex behaviours related to sleep, depression,
addiction and anxiety,” says co-principal investigator Michael R.
Bruchas, PhD, assistant professor of anesthesiology at Washington
University. “Understanding which populations of neurons are involved
in these complex behaviours may allow us to target specific brain
cells that malfunction in depression, pain, addiction and other
disorders.”

Although a number of important pathways in the brain can be
studied with optogenetics, many neuroscientists have struggled with
the engineering challenge of delivering light to precise locations
deep in the brain. Most methods have tethered animals to lasers with
fibre optic cables, limiting their movement and altering natural
behaviours.

But with the new devices, the mice freely moved about and were
able to explore a maze or scamper on a wheel. The electronic LEDs
are housed in a tiny fibre implanted deep in the brain. That’s
important to the device’s ability to activate the proper neurons,
according to John A. Rogers, PhD, professor of materials science and
engineering at the University of Illinois.

“You want to be able to deliver the light down into the depth of
the brain,” Rogers says. “We think we’ve come up with some powerful
strategies that involve ultra-miniaturized devices that can deliver
light signals deep into the brain and into other organs in the
future.”

Using light from the cellular-scale LEDs to stimulate
dopamine-producing cells in the brain, the investigators taught the
mice to poke their noses through a specific hole in a maze. Each
time a mouse would poke its nose through the hole, that would
trigger the system to wirelessly activate the LEDs in the implanted
device, which then would emit light, causing neurons to release
dopamine, a chemical related to the brain’s natural reward system.

“We used the LED devices to activate networks of brain cells that
are influenced by the things you would find rewarding in life, like
sex or chocolate,” says co-first author Jordan G. McCall, a
neuroscience graduate student in Washington University’s Division of
Biology and Biomedical Sciences. “When the brain cells were
activated to release dopamine, the mice quickly learned to poke
their noses through the hole even though they didn’t receive any
food as a reward. They also developed an associated preference for
the area near the hole, and they tended to hang around that part of
the maze.”

The researchers believe the LED implants may be useful in other
types of neuroscience studies or may even be applied to different
organs. Related devices already are being used to stimulate
peripheral nerves for pain management. Other devices with LEDs of
multiple colours may be able to activate and control several neural
circuits at once.

In addition to the tiny LEDs, the devices also carry miniaturized
sensors for detecting temperature and electrical activity within the
brain. Bruchas and his colleagues already have begun other studies
of mice, using the LED devices to manipulate neural circuits that
are involved in social behaviours. This could help scientists better
understand what goes on in the brain in disorders such as depression
and anxiety.

“We believe these devices will allow us to study complex stress
and social interaction behaviours,” Bruchas explains. “This
technology enables us to map neural circuits with respect to things
like stress and pain much more effectively.”